Biological activity of aspartic proteinase inhibitors related to pepstatin.
We have synthesized eight tripeptide analogs of pepstatin in which both the side-chain and stereochemistry of the novel amino acid statine have been altered. They have been compared to pepstatin for inhibition of pepsin and cathepsin D activity, inhibition of autolysis at pH 4, and inhibition of protein degradation in cultured cells. Effective inhibition of aspartic proteinase activity appears to require the novel amino acid to have a bulky hydrophobic side-chain and the S-configuration at both chiral centers. However, the Cbz-Val-Val-(3S4S)-statine peptide was more effective than pepstatin in cultured cells, and inhibition was also achieved, and in some cases enhanced relative to pepstatin, by its stereoisomers and by tripeptides containing valyl and alanyl analogs of statine.
D000596:Amino Acids; D000605:Amino Alcohols; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010434:Pepsin A / Q000037:antagonists & inhibitors; D010436:Pepstatins / Q000494:pharmacology*; D011480:Protease Inhibitors; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000605:Amino Alcohols; D007328:Insulin; D009842:Oligopeptides; D010436:Pepstatins; D011480:Protease Inhibitors; D002403:Cathepsins; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A; D002402:Cathepsin D; C013165:statine